Interleukin-1 signaling is initiated by recruitment of
adapter proteins and kinases to the type I interleukin-1 receptor (IL-1RI). It is modulated by accompanying
redox processes at various levels, such as (auto-)
phosphorylation of the IL-1RIassociated kinase
IRAK, the phosphorylation of IκB and translocation
and transcriptional activity of NFκB. Here we demonstrate
that the thiolmodifying agents diamide, menadione,
and phenylarsine oxide (PAO) block the recruitment
of IRAK to the receptor without inhibiting kinase
activity in the immunoprecipitated IL-1RI complex in
the human epithelial cell line ECV304 and the murine T
cell line EL-4. Inhibition of IRAK receptor association
by menadione is reversible in a GSH-dependent manner,
while the PAO effect proved to be irreversible.
Phospholipid hydroperoxide glutathione peroxidase
attenuates inhibition by menadione. Recruitment correlates
with the presence of thiol groups in IRAK that
were available for IAIT-labeling. We conclude that recruitment
of IRAK to the IL-1RI is redox regulated by
the glutathione system, a reduced status being a prerequisite
for an appropiate IL-1 response.
Biological Chemistry keeps you up-to-date with the latest advances in the molecular life sciences. The journal publishes Research Articles, Short Communications, Reviews and Minireviews. Areas include: general biochemistry/pathobiochemistry, structural biology, molecular and cellular biology, genetics and epigenetics, virology, molecular medicine, plant molecular biology/biochemistry and novel experimental methodologies.